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1.
BMC Public Health ; 22(1): 1470, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35915479

RESUMO

BACKGROUND: Regular testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an important strategy for controlling virus outbreaks on university campuses during the COVID-19 pandemic but testing participation rates can be low. The Residence-Based Testing Participation Pilot (RB-TPP) was a novel intervention implemented at two student residences on a large UK university campus over 4 weeks. The aim of the pilot was to increase the frequency of asymptomatic SARS-CoV-2 saliva testing onsite. This process evaluation aimed to determine whether RB-TPP was implemented as planned and identify implementation barriers and facilitators. METHODS: A mixed-methods process evaluation was conducted alongside the RB-TPP. Evaluation participants were students (opting in, or out of RB-TPP) and staff with a role in service provision or student support. Monitoring data were collected from the intervention delivery team and meeting records. Data were collected from students via online survey (n = 152) and seven focus groups (n = 30), and from staff via individual interviews (n = 13). Quantitative data were analysed descriptively and qualitative data thematically. Barriers and facilitators to implementation were mapped to the 'Capability, Opportunity, Motivation-Behaviour' (COM-B) behaviour change framework. RESULTS: Four hundred sixty-four students opted to participate in RB-TPP (98% of students living onsite). RB-TPP was implemented broadly as planned but relaxed social distancing was terminated early due to concerns relating to national escalation of the COVID-19 Delta variant, albeit testing continued. Most students (97.9%) perceived the period of relaxed social distancing within residences positively. The majority engaged in asymptomatic testing (88%); 46% (52% of testers) were fully compliant with pre-determined testing frequency. Implementation was facilitated by convenience and efficiency of testing, and reduction in the negative impacts of isolation through opportunities for students to socialise. Main barriers to implementation were perceived mixed-messages about the rules, ambivalent attitudes, and lack of adherence to COVID-19 protective measures in the minority. CONCLUSIONS: This process evaluation identifies factors that help or hinder the success of university residence-based outbreak prevention and management strategies. RB-TPP led to increased rates of SARS-CoV-2 testing participation among students in university residences. Perceived normalisation of university life significantly enhanced student mental wellbeing. The complexity and challenge generated by multiple lines of communication and rapid adaptions to a changing pandemic context was evident. TRIAL REGISTRATION NUMBER: UKAS 307727-02-01; Pre-results. CLINICALTRIALS: gov Identifier: NCT05045989 ; post-results (first posted, 16/09/21). ETHICAL APPROVAL: Faculty of Medicine & Health Sciences Research Ethics Committee, University of Nottingham (Ref: FMHS 96-0920).


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Teste para COVID-19 , Humanos , Pandemias/prevenção & controle , Reino Unido/epidemiologia , Universidades
2.
Gynecol Obstet Fertil Senol ; 50(2): 142-150, 2022 Feb.
Artigo em Francês | MEDLINE | ID: mdl-34562643

RESUMO

INTRODUCTION: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions (ABL)". Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. METHODS: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. RESULTS: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, P<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). CONCLUSION: Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.


Assuntos
Ansiedade , Neoplasias da Mama , Ansiedade/diagnóstico , Ansiedade/psicologia , Mama , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Estudos Prospectivos , Inquéritos e Questionários
3.
Mol Biol Cell ; 32(20): ar10, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34379441

RESUMO

Mutations in the genes that encode α- and ß-tubulin underlie many neurological diseases, most notably malformations in cortical development. In addition to revealing the molecular basis for disease etiology, studying such mutations can provide insight into microtubule function and the role of the large family of microtubule effectors. In this study, we use budding yeast to model one such mutation-Gly436Arg in α-tubulin, which is causative of malformations in cortical development-in order to understand how it impacts microtubule function in a simple eukaryotic system. Using a combination of in vitro and in vivo methodologies, including live cell imaging and electron tomography, we find that the mutant tubulin is incorporated into microtubules, causes a shift in α-tubulin isotype usage, and dramatically enhances dynein activity, which leads to spindle-positioning defects. We find that the basis for the latter phenotype is an impaired interaction between She1-a dynein inhibitor-and the mutant microtubules. In addition to revealing the natural balance of α-tubulin isotype utilization in cells, our results provide evidence of an impaired interaction between microtubules and a dynein regulator as a consequence of a tubulin mutation and sheds light on a mechanism that may be causative of neurodevelopmental diseases.


Assuntos
Dineínas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Tubulina (Proteína)/genética , Dineínas/genética , Tomografia com Microscopia Eletrônica/métodos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Microtúbulos/metabolismo , Mutação , Transtornos do Neurodesenvolvimento/metabolismo , Neurogênese , Fenótipo , Receptores Mitogênicos/genética , Receptores Mitogênicos/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomycetales/metabolismo , Fuso Acromático/metabolismo , Tubulina (Proteína)/metabolismo
4.
Med Trop (Mars) ; 70(1): 13-7, 2010 Feb.
Artigo em Francês | MEDLINE | ID: mdl-20337109

RESUMO

The purpose of this report is to describe the experience of a specialized medico-surgical ENT team sent to hospital centers in Atalaha and Tulear, Madagascar by a nonprofit organization called "Terre rouge" from the Reunion Island. In three separate short-term missions, a total of 93 patients received care. Discussion focuses on the particular pathological, cultural, and pedagogical features of the Island and on the resources that were deployed during the missions. Providing ENT care in district hospitals in Madagascar requires adaptation to the difficult climatic conditions, poor hospital facilities (infrastructure, equip ment, and personnel), and advanced stage of diseases. To ensure continuous access to ENT care, it will be necessary to provide practical and didactic training for healthcare personnel in the country.


Assuntos
Missões Médicas , Otorrinolaringopatias/terapia , Equipe de Assistência ao Paciente , Feminino , Hospitais de Distrito , Humanos , Madagáscar , Masculino , Organizações sem Fins Lucrativos , Estudos Retrospectivos
5.
Acta Biol Hung ; 60(1): 79-88, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19378926

RESUMO

The research was conducted to investigate the toxic effects of cadmium chloride (CdCl2), administered during gestation period on female Wistar rats. Pregnant rats received CdCl2 (20 mg/l, orally) from Day 6 to Day 19 of pregnancy. Results showed that Cd treatment induced a decrease in body weight gain. The relative liver weight increased significantly, with a marked decrease of glycogen and total lipids content. The administration of Cd induced hepatotoxicity as indicated by elevations in plasma alanine aminotransferase (ALT), aspartate aminotransferase and lactate dehydrogenase (LDH) activities (p < 0.05). Treatment with CdCl2 caused a significant (p < 0.05) increase in glucose. A significant increase was observed in the level of MDA and 8-oxodGuo tissues in the cadmium-exposed group compared to the control group (p < 0.05). Results showed that cadmium given to dams led to an oxidative stress and DNA damage in tissues of pregnant rats.


Assuntos
Cloreto de Cádmio/toxicidade , Dano ao DNA/efeitos dos fármacos , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Administração Oral , Alanina Transaminase/metabolismo , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Cádmio/toxicidade , Cloreto de Cádmio/administração & dosagem , Intoxicação por Cádmio/metabolismo , Intoxicação por Cádmio/patologia , Feminino , Rim/metabolismo , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Fígado/patologia , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Ratos , Ratos Wistar , Aumento de Peso/efeitos dos fármacos
6.
Lab Chip ; 8(10): 1713-22, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18813395

RESUMO

DNA repair mechanisms constitute major defences against agents that cause cancer, degenerative disease and aging. Different repair systems cooperate to maintain the integrity of genetic information. Investigations of DNA repair involvement in human pathology require an efficient tool that takes into account the variety and complexity of repair systems. We have developed a highly sensitive damaged plasmid microarray to quantify cell lysate excision/synthesis (ES) capacities using small amounts of proteins. This microsystem is based on efficient immobilization and conservation on hydrogel coated glass slides of plasmid DNA damaged with a panel of genotoxic agents. Fluorescent signals are generated from incorporation of labelled dNTPs by DNA excision-repair synthesis mechanisms at plasmid sites. Highly precise DNA repair phenotypes i.e. simultaneous quantitative measures of ES capacities toward seven lesions repaired by distinct repair pathways, are obtained. Applied to the characterization of xeroderma pigmentosum (XP) cells at basal level and in response to a low dose of UVB irradiation, the assay showed the multifunctional role of different XP proteins in cell protection against all types of damage. On the other hand, measurement of the ES of peripheral blood mononuclear cells from six donors revealed significant diversity between individuals. Our results illustrate the power of such a parallelized approach with high potential for several applications including the discovery of new cancer biomarkers and the screening of chemical agents modulating DNA repair systems.


Assuntos
Reparo do DNA , Plasmídeos , Linhagem Celular Transformada , Células HeLa , Humanos , Espectrometria de Fluorescência
7.
Eur Respir J ; 31(5): 1046-53, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18256067

RESUMO

Antioxidant counteraction of oxidative stress has been poorly explored in obstructive sleep apnoea (OSA). Serum albumin is a major antioxidant agent and structural modifications induced by glucose or free radicals impair its antioxidant properties. The aim of the present study was to compare antioxidant capacities and structural changes of albumin in nonobese OSA patients and healthy volunteers. Albumin structural changes were studied by quenching of fluorescence in the presence of acrylamide. Albumin thiols and fructosamines, reflecting oxidation- and glycation-induced changes in serum albumin, respectively, were assessed. Albumin structural changes were demonstrated by a significant decrease in quenching of fluorescence in OSA patients. Oxidation, resulting in a significant decrease in thiol groups (3.7+/-0.7 versus 2.3+/-0.4 micromol x g(-1) protein), and glycation, associated with a significant increase in fructosamines (226.6+/-27 versus 286+/-44.4 micromol x L(-1)), were found when comparing healthy volunteers with OSA patients. There was a significant relationship between both parameters and sleep apnoea severity. After continuous positive airway pressure intervention, albumin thiol groups were reassessed in seven of the 16 OSA patients and increased significantly from 2.25+/-0.39 to 2.79+/-0.31 micromol x g(-1) protein. Obstructive sleep apnoea patients demonstrated a reduction in serum albumin antioxidant properties that may aggravate oxidative stress and, thus, contribute to cardiovascular and metabolic morbidities.


Assuntos
Antioxidantes/farmacologia , Albumina Sérica/farmacologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Antioxidantes/química , Antioxidantes/metabolismo , Estudos de Casos e Controles , Pressão Positiva Contínua nas Vias Aéreas , Frutosamina/sangue , Glicosilação , Humanos , Isoprostanos/urina , Pessoa de Meia-Idade , Oxirredução , Albumina Sérica/química , Albumina Sérica/metabolismo , Apneia Obstrutiva do Sono/sangue , Compostos de Sulfidrila/sangue
8.
Diabetes Metab ; 34(2): 148-54, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18329309

RESUMO

OBJECTIVE: Fructose consumption is increasing worldwide and is likely to play a role in metabolic disorders. Dietary fructose is often recommended for diabetic patients, as this form of carbohydrate leads to a lower postprandial rise in plasma glucose and insulin. However, fructose contributes to the generation of free radicals. The aim of this work was to investigate the acute effects of a fructose load in patients with type 2 diabetes mellitus (T2DM), compared with healthy controls, on several metabolic oxidative biomarkers, particularly plasma 15-F2t isoprostanes (15-F2t isoPs). RESEARCH DESIGN AND METHODS: Six T2DM patients and six healthy subjects were recruited. All patients underwent a single fructose tolerance test (75 g of anhydrous fructose). Plasma 15-F2t isoPs concentrations, plasma total antioxidant capacity (TAS) and thiobarbituric acid reactive substances (TBARS) were measured at baseline, and at 60, 120, 180 and 240 min after fructose absorption. RESULTS: Baseline plasma 15-F2t isoPs concentrations were significantly increased in T2DM patients compared with controls (310+/-47 versus 237+/-20 pg/mL, respectively; P<0.01) and rose significantly (P<0.01) to 414+/-45 pg/mL in diabetic patients. No change in TAS or TBARS was observed in either group. CONCLUSION: Plasma 15-F2t isoPs are increased during acute fructose loading in T2DM. Knowing the potentially deleterious effect of plasma 15-F2t isoPs-in particular, vascular lesions-and in light of our results, it is necessary to reconsider fructose consumption in T2DM patients, as we can now show, for the first time, a possible association between acute fructose loading and deleterious effects in such patients.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Dinoprosta/análogos & derivados , Frutose/farmacologia , Adulto , Glicemia/análise , Índice de Massa Corporal , Colesterol/sangue , Dinoprosta/sangue , Jejum , Feminino , Humanos , Lactatos/sangue , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Valores de Referência , Triglicerídeos/sangue
9.
Eur J Clin Nutr ; 62(10): 1155-61, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17622261

RESUMO

OBJECTIVE: To measure the correlations between habitual intakes of individual n-6 and n-3 polyunsaturated fatty acids (PUFA) and their percentages in total plasma fatty acids in a population of adult men and women. SUBJECTS/METHODS: Two hundred and seventy-six men and 257 women aged 45-60 (men) or 35-60 (women) at baseline, volunteers of the French SU.VI.MAX cohort. Fifteen 24-h record questionnaires were used to estimate the habitual intake of energy, total fat and linoleic, alpha-linolenic acid, arachidonic, eicosapentaenoic (EPA), n-3 docosapentaenoic (DPA) and docosahexaenoic (DHA) acids. Fatty acid composition of fasting plasma total lipids has been determined at baseline. RESULTS: Dietary intakes of linoleic acid, arachidonic acid, EPA and DHA were weakly but significantly correlated (0.16

Assuntos
Dieta , Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Adulto , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Gorduras Insaturadas na Dieta/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Comportamento Alimentar , Feminino , França , Humanos , Ácido Linoleico/administração & dosagem , Ácido Linoleico/metabolismo , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Ácido alfa-Linolênico/administração & dosagem , Ácido alfa-Linolênico/metabolismo
10.
Ann Biol Clin (Paris) ; 65(4): 393-8, 2007.
Artigo em Francês | MEDLINE | ID: mdl-17627920

RESUMO

Total plasma homocysteine emerged in the past few years as an independent risk factor for cardiovascular diseases. This test is now currently prescribed for the diagnosis of unexplained thrombosis in young adults or recurrent thrombosis in patients with arteriopathy. This sulphured amino-acid is an important intermediate in transsulfuration and remethylation pathways of methionine metabolism. Within the context of a collaboration between Monastir and Grenoble Universities and because a gas chromatograph mass spectrometer (GC-MS) instrument was available in Monastir, we proposed to transpose a GC-MS method previously developed in Grenoble's hospital for this parameter and to validate it by comparison with the liquid chromatography tandem mass spectrometry (LC-MS-MS) method, used at present. Analytical performances were good: detection limit 0.4 micromol/L and linear range up to 4 mg/L (29.6 micromol/L), and between-run and within-run precision with coefficients of variation < 5% and < 8 %, respectively. The comparison with LC-MS-MS method showed a good correlation (y = 0.9874 x -0.208; r(2) = 0.84). Mean difference from LC-MS-MS was -0.4 micromol/L. Plasma concentrations of homocysteine (mean + SD) determined among Tunisian adults, 29 men, 27 women, of the same age were respectively: 11.6 +/- 2.4 micromol/L and 10.1 +/- 2.7 micromol/L, p = 0.025. This method is now currently used to evaluate tHcy concentration in patients with risk factors for cardiovascular disease.


Assuntos
Homocisteína/sangue , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Espectrometria de Massas , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Trombose/epidemiologia , Tunísia
12.
Eur J Clin Nutr ; 60(6): 706-17, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16391586

RESUMO

OBJECTIVES: The data was collected during the inclusion step of the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) study. This article deals with the study's first stage before any supplementation. The collected data shows factors influencing blood vitamin concentrations and may reflect the vitamin status of volunteers. MATERIAL AND METHODS: A total of 12,741 volunteers were enrolled in the SU.VI.MAX study 7,713 women 35-60 years of age and 5,028 men 50-60 years of age. The serum concentrations of retinol, alpha-tocopherol, and beta-carotene were measured by HPLC, and vitamin C concentration was measured by spectrofluorimetry using a Technicon continuous flow analysis apparatus. The volunteers recorded their 24 h diet by means of a specific terminal that was connected to the main central computer of the SU.VI.MAX study. Volunteers recorded the food they consumed daily and estimated its quantity by comparing pictures of dishes. RESULTS: Retinol concentration was significantly higher in older volunteers, and was higher in male than in female volunteers. Smoking had no effect on serum retinol, but the latter was higher in the autumn than in the winter. Serum retinol concentrations were higher in the Southwest region and lower in the Ile-de-France and East-Centre regions. Serum alpha-tocopherol was slightly higher in older volunteers and also higher in male volunteers. Serum alpha-tocopherol was significantly lower in smokers, and former smokers showed intermediate levels. Like retinol, serum alpha-tocopherol was higher in the autumn, and higher in the Southwest as compared to the East-Centre Serum beta-carotene was slightly higher in younger volunteers, and concentrations were higher in female than in male volunteers. Tobacco smoking decreased serum beta-carotene, which was higher in the autumn, and higher in the East, West, and North regions. Serum vitamin C was higher in female volunteers, and was not age related. Serum vitamin C was lower in smokers, was season-dependant, but contrary to fat-soluble vitamins, concentrations were higher in the winter and spring. Serum vitamin C was higher in the Southeast and East-Centre, but lower in the North region. CONCLUSION: These results suggest that serum retinol concentrations depend on gender, age, seasons, and location of residence. Similarly, serum alpha-tocopherol concentrations were slightly influenced by age, but more by tobacco smoking, seasons, dietary intake, and location of residence. Serum concentrations of beta-carotene depend on gender, age, smoking status, dietary intake, and location of residence. Serum vitamin C concentrations depend on gender, age, smoking status, seasons, dietary intake, and location of residence. Contrary to beta-carotene, retinol concentrations were higher in male than in female volunteers. Such a reversed relation suggests a higher beta-carotene-retinol conversion in male volunteers.


Assuntos
Antioxidantes/metabolismo , Ácido Ascórbico/sangue , Dieta , Vitamina A/sangue , alfa-Tocoferol/sangue , beta Caroteno/sangue , Adulto , Fatores Etários , Análise de Variância , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Demografia , Registros de Dieta , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estações do Ano , Fatores Sexuais , Fumar , Vitamina A/administração & dosagem , alfa-Tocoferol/administração & dosagem , beta Caroteno/administração & dosagem
13.
Arch Mal Coeur Vaiss ; 99(7-8): 665-8, 2006.
Artigo em Francês | MEDLINE | ID: mdl-17061440

RESUMO

The object of this work was to determine the risk of hypertension after 6.5 years'- follow-up of supplementation in vitamins and antioxidant minerals at nutritional doses in the SU.VI.MAX trial. The authors also studied the association with plasma concentrations of antioxidants at inclusion and at long term. This was a randomised nutritional primary prevention study including 5086 adults of the SU.VI.MAX trial. After 6.5 years' follow-up, no effect of supplementation on the risk of developing hypertension could be shown compared with the placebo group: odds ratios (OR IC 95%): 1.04 (0.87-1.23) in men and 1.10 (0.95-1.29) in women. Besides, in the male 2nd and 3rd tertiles of serum beta-carotene levels at inclusion the risk of hypertension was lower [multivariate OR: 0.70 (0.44-1.12) and 0.53 (0.33-0.86) for placebo, and 0.59 (0.37-0.94) and 0.67 (0.42-1.07) for the supplemented groups]. The authors conclude that, despite a reverse relationship in men between the plasma concentrations of beta-carotene and the risk of hypertension, supplementation in antioxidants at nutritional doses had no effect on the risk of developing hypertension after 6.5 years' follow-up.


Assuntos
Antioxidantes/uso terapêutico , Suplementos Nutricionais , Hipertensão/epidemiologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , beta Caroteno/sangue
14.
Rev Med Interne ; 27(2): 140-3, 2006 Feb.
Artigo em Francês | MEDLINE | ID: mdl-16298022

RESUMO

INTRODUCTION: To the request of total plasma homocysteine determination in the investigation of vascular disease, diagnosis of homocystinuria in young adult patients with mild phenotype is not so rare. EXEGESIS: A 26-year-old man developed embolic cerebral infarction and a 22-year-old woman presented a right renal venous thrombosis one week after delivery. In each case, high concentration of total plasma homocysteine was first found and plasma and urinary amino acids analysis later on directed the diagnosis towards homocystinuria. Finally, reduced skin fibroblast cystathionine beta-synthase activity confirmed the diagnosis of homocystinuria. CONCLUSION: Total plasma homocysteine determination must be determined for screening for hyperhomocysteinemia in young adults with venous thromboembolism without characteristic phenotypic features of homocystinuria.


Assuntos
Homocistinúria/complicações , Homocistinúria/diagnóstico , Hiper-Homocisteinemia/etiologia , Adulto , Idade de Início , Feminino , Humanos , Hiper-Homocisteinemia/patologia , Masculino , Fenótipo , Índice de Gravidade de Doença , Trombose Venosa/etiologia
15.
Ann Pharm Fr ; 64(6): 390-6, 2006 Nov.
Artigo em Francês | MEDLINE | ID: mdl-17119468

RESUMO

Oxidative stress is an abnormal phenomenon occurring inside our cells or tissues when production of oxygen radicals exceeds their antioxidant capacity. Excess of free radicals damage essential macromolecules of the cell, leading to abnormal gene expression, disturbance in receptor activity, proliferation or cell dye, immunity perturbation, mutagenesis, protein or lipofushin deposition. Numerous human diseases involve during the pathological process such a stress, localized or general (in the same way as inflammation). In many serious diseases such as cancer, ocular degeneration (age related macular degeneration or cataract), neurodegenerative diseases (ataxia, amyotrophic lateral sclerosis, Alzheimer's disease) stress is the factor original. In familial amyotrophic lateral sclerosis the genetic abnormality occurred an abnormal coding for an antioxidant enzyme, copper-zinc super oxide dismutase. In various other diseases oxidative stress occur secondary to the initial disease but plays an important in role immune or vascular complications. This is the case in infectious disease such as AIDS or septic shock, Parkinson's disease or renal failure. So antioxidant treatment seems logical to be tested in these pathologies. But they have to be applied early in the process, before irreversible mechanisms. They need also to be prescribed at low doses as baseline free radical production have to be preserved to maintain useful activity that cannot be suppressed.


Assuntos
Doença , Estresse Oxidativo/fisiologia , Humanos , Oxidantes/metabolismo
16.
Biochim Biophys Acta ; 1209(2): 260-4, 1994 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-7811700

RESUMO

We have previously reported that zinc deficiency could increase in vivo lipid peroxidation and decrease rat insulin sensitivity. In the present paper, we address the hypothesis of the role of zinc on insulin molecule in relation to free radical damage. From native recombinant human insulin, we prepared a zinc-depleted insulin. Both preparations were subjected to controlled free radical attack by incubation in the presence of 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH). To obtain minimally oxidized insulin, the oxidation process was monitored by measuring the intrinsic fluorescence of the insulin preparations. For 2.5 mM of AAPH, the autofluorescence of zinc-depleted insulin markedly decreased as compared to that of native insulin. These data are in favor of conformational changes of the insulin molecule which were further studied by quenching of fluorescence by means of potassium iodide. Using the euglycaemic hyperinsulinic glucose clamp technique in rats, the in vivo activities of the different insulin preparations, showed that oxidized zinc-depleted insulin had a marked reduced activity as compared to oxidized native insulin. From our results, we suggest that structural modification of the insulin molecule took place after zinc depletion and free radical treatment. Moreover, zinc depletion appeared to increase the susceptibility of insulin to free radicals.


Assuntos
Radicais Livres , Insulina/química , Zinco/farmacologia , Animais , Técnica Clamp de Glucose , Humanos , Insulina/fisiologia , Masculino , Ratos , Ratos Wistar , Proteínas Recombinantes/química , Zinco/deficiência
17.
Diabetes ; 48(2): 353-7, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10334313

RESUMO

Recently there has been growing interest in the effects of antioxidants on insulin activity. In the present study, we investigated the effect of metformin on free radical activity and insulin sensitivity in high fructose-fed rats, a diet that leads to insulin resistance. The animals were divided into four groups (n = 16 per group; experiment duration = 6 weeks): the control (C) group received a standard diet; the control metformin (CM) group was fed a control diet and received metformin (200 mg x kg(-1) x day(-1) in water); the fructose control (FT) group was fed a diet in which fructose composed 56.8% of the total carbohydrates; and the fructose metformin (FM) group received high-fructose diet and metformin (200 mg x kg(-1) x day(-1) in water). The glucose clamp technique was used to determine insulin sensitivity in eight animals per group. Metabolic and oxidative stress parameters were measured in the remaining rats. In the FT rats, insulin resistance, lower red cell CuZn superoxide dismutase activity and lower blood reduced glutathione were observed. Metformin treatment improved both the insulin activity and the antioxidant defense system. In the CM group, metformin had no effect on metabolic parameters, but improved red cell antioxidant enzyme activities and the blood GSH level, which suggests that it has an antioxidant activity independent of its effect on insulin activity.


Assuntos
Carboidratos da Dieta/administração & dosagem , Sequestradores de Radicais Livres/metabolismo , Frutose/administração & dosagem , Hipoglicemiantes/farmacologia , Insulina/fisiologia , Metformina/farmacologia , Animais , Carboidratos da Dieta/farmacologia , Frutose/farmacologia , Peróxidos Lipídicos/metabolismo , Masculino , Oxirredutases/sangue , Ratos , Ratos Wistar
18.
Curr Top Microbiol Immunol ; 272: 37-55, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12747546

RESUMO

Each of the 12 vertices of the adenovirus virion is made of penton, the complex of two oligomeric proteins: a pentameric penton base anchored in the capsid and an antenna-like trimeric fiber extending outwards. Adenovirus penton plays an essential role in the infection of host cells because it is indispensable for virus attachment and internalization. The initial interactions of penton with the primary and secondary receptors are well described. In contrast with that, the role of the penton components downstream of the initial cell contact is not known. This work shows for the first time that two adenovirus structural proteins, fiber and base, are able to interact intimately with different classes of cellular targets. In the case of penton base, a protein responsible for virus internalization, the partners include three ubiquitin-protein ligases that are involved in protein turnover, cell cycle control and endocytosis. Another base protein partner, BAG3, is involved in controlling Hsc70 chaperone activity. Virus attachment protein, fiber, interacts with many different partners, some of them involved in signal transduction and cell growth. Further work will illustrate the implications of these interactions for both the viral and cellular life cycles.


Assuntos
Adenoviridae/fisiologia , Proteínas do Capsídeo , Capsídeo/metabolismo , Proteínas Virais/metabolismo , Adenoviridae/química , Adenoviridae/ultraestrutura , Capsídeo/química , Humanos , Receptores Virais/metabolismo , Proteínas Virais/química
19.
Eur J Clin Nutr ; 59(10): 1181-90, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16034362

RESUMO

OBJECTIVE: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc. METHODS: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study. RESULTS: Women had higher baseline serum beta-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum beta-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum beta-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum beta-carotene and higher selenium concentrations. Serum beta-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary beta-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum beta-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. CONCLUSION: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients.


Assuntos
Antioxidantes/metabolismo , Dieta , Obesidade/sangue , Oligoelementos/sangue , Adulto , Fatores Etários , Consumo de Bebidas Alcoólicas/sangue , Antioxidantes/administração & dosagem , Antioxidantes/análise , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/sangue , Análise Química do Sangue , Ingestão de Energia , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Selênio/administração & dosagem , Selênio/sangue , Fatores Sexuais , Fumar/sangue , Oligoelementos/administração & dosagem , Oligoelementos/análise , Vitamina E/administração & dosagem , Vitamina E/sangue , Zinco/administração & dosagem , Zinco/sangue , beta Caroteno/administração & dosagem , beta Caroteno/sangue
20.
Med Chem ; 1(6): 629-33, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16787346

RESUMO

Resveratrol, a polyphenolic phytoalexin, is a very effective antioxidant that also exhibits strong antiproliferative and anti-inflammatory properties. Recent studies have provided support for the use of resveratrol in human cancer chemoprevention, in combination with either chemotherapeutic drugs or cytotoxic factors for a most efficient treatment of drug refractory tumor cells. Resveratrol is also widely used in topical preparations, as a chemoprotective compound against development of several cutaneous disorders, including skin cancer. Nevertheless, the combined effect of resveratrol and UVA irradiation on cellular toxicity and DNA damage has never been assessed. The aim of this work was to investigate the effect of resveratrol on cell fate in immortalized human keratinocytes HaCaT cells. The results indicated that resveratrol potentiates the production of significant amounts of 8-oxo-7,8-dihydro-2'-deoxyguanosine in UVA-irradiated genomic DNA. Moreover, the combination of resveratrol with UVA significantly enhances the induction of DNA strand breaks and cell death in HaCaT keratinocytes. The conclusion is a potential hazardous effect of topical application of resveratrol, particularly on regions exposed to sunlight.


Assuntos
Dano ao DNA , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Estilbenos/farmacologia , Raios Ultravioleta , 8-Hidroxi-2'-Desoxiguanosina , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA/efeitos dos fármacos , DNA/genética , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biossíntese , Desoxiguanosina/efeitos da radiação , Humanos , Queratinócitos/metabolismo , Radiossensibilizantes/farmacologia , Resveratrol , Relação Estrutura-Atividade
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